A program is proposed to investigate the process of biological calcification, with specific emphasis on the role of collagen. The two major objectives of the program are: (1) to determine whether mineral nucleation by collagen itself might be an in vivo regulating factor in the calcification process, and (2) to define in physico-chemical terms the heterogeneous nucleation of mineralization by collagen. Similarly treated collagens from the skin, tail tendon, bone, and possibly dentin of the lathyritic rat will be compared with regard to: (1) mineral nucleation by the reconstituted proteins, and (2) interaction of the soluble proteins with aqueous mineralizing solutions. Both studies will extend to fractionated collagen systems. Nucleation kinetics will be determined for reconstituted collagens and evaluated on the basis of control studies using decalcified bone and dentin. The interaction of soluble protein with aqueous calcium phosphate will be examined for: (1) specific ion binding using electrophoresis, and (2) the involvement of certain protein groups, using nuclear magnetic resonance.